Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Feb 2007
Novel mechanisms of platinum drug resistance identified in cells selected for resistance to JM118 the active metabolite of satraplatin.
The goal of this study was to identify molecular determinants of sensitivity and resistance to JM118, the active metabolite of satraplatin, an orally bioavailable cisplatin analog that has activity in prostate cancer. ⋯ While the cellular defense mechanisms that protect cells against JM118 also mediate resistance to the other Pt drugs, these mechanisms are quite different from those commonly found in cells selected for resistance to cisplatin. JM118-resistant cells accumulate more rather than less Pt and rely on an intracellular detoxification mechanism different from that involved in cisplatin resistance. This is consistent with clinical evidence suggesting that satraplatin has activity in diseases in which cisplatin does not. In this model, JM118 resistance is associated with substantial collateral hypersensitivity to docetaxel, paclitaxel, and doxorubicin.
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Cancer Chemother. Pharmacol. · Feb 2007
Reproductive toxicity evaluation of a new camptothecin anticancer agent, CKD-602, in pregnant/lactating female rats and their offspring.
CKD-602 is a camptothecin anticancer agent that was recently developed by the Chong Kun Dang Pharmaceutical Co. (Seoul, Korea). This study examined the potential adverse effects of CKD-602 on pregnancy, delivery, and lactation in female Sprague-Dawley rats as well as on the pre- and postnatal development of their offspring. One hundred pregnant females were divided into four groups: three treatment groups and a control group. ⋯ In the medium dose group, only slight maternal toxicity including suppressed body weight and decreased food consumption was observed. There were no treatment-related effects on the maternal function and pre- and postnatal development in the low dose group. The no-observed-adverse-effect level (NOAEL) of CKD-602 for the dams are considered to be 5.7 microg/kg/day, however, the NOAEL for their offspring are estimated to be 17 microg/kg/day.